Endogenous material - C0 is not eq zero

Dear Users! I tried to describe the PK of an endogenous material. I started from the example in UG VIII but after I realize that this method is not so good for me, because the amount measured in the central compartment is not the object of the DADTs. Instead of, the dadt describes a system that adjust the amount in the compartment against the so called base line level, therefore A(1) can be negative!!! Is there any method that treats situation when the C0 is not zero (I also interested to estimate C0 somehow). Thanks, István István Németh PhD Biostatistician Developmental Drug Metabolism & Pharmacokinetics Pharmacological and Drug Safety Research Gedeon Richter Plc Tel: 00 36 1 505 7082 Fax: 00 36 1 889 8526

Dear Istvan, If you assume the production of the endogenous compound is zero-order process and, at baseline, your system is at steady-state, then you may want to try a code like what I paste below for one comp IV model. $PK BSL = THETA(1) * ETA(1) ;C0 in conc units CL = THETA(2) * ETA(2) KEND = BSL*CL V = THETA(3) * ETA(3) KEL = CL/V $DES DADT(1) = KEND - KEL*A(1) As far as the assumptions hold, the approach that "is not so good for you" should provide very similar results than the one just mentioned above for linear models, such one comp model. For non-linear models, such target mediated disposition model, the approach suggested above should work better. Hope it helps, Juanjo.

István, You may also want to try using ;initialize the central cmt with baseline concentration ;PRC is a variable in my dataset that contains the baseline ;concentration of the "endogenous" substance (modeled as dadt(3) in my case). VC is the parameter that describes the volume of the compartment. IF(A_0FLG.EQ.1) THEN A_0(3)=PRC*VC ENDIF ;You can also set A_0(n) variables to a theta value or other expression. ;In an example similar to Juan Jose's: DADT(1) = PRATE - K10*A(1) ;where PRATE=production rate of endogenous substance in mg/hr ;at steady-state PRATE=K10*A(1) or A(1) = PRATE/K10 PRATE=THETA(1)*EXP(ETA(1)) K10=THETA(2)*EXP(ETA(2) IF(A_0FLG.EQ.1) THEN A_0(1)=PRATE/K10 ENDIF You can read more about this under the help topic: COMPARTMENT INITIALIZATION BLOCK. I've included the first couple of paragraphs below. Best regards, Luann Phillips Director, PK/PD Cognigen Corporation ___________________________________________________________________ | | | COMPARTMENT INITIALIZATION BLOCK | |_________________________________________________________________| DISCUSSION: A "compartment initialization block" is a block of abbreviated code that sets the initial state of the kinetic system. It is to be exe- cuted only when A_0FLG=1. Such a block may be present only in $PK. PREDPP sets A_0FLG to 1 at a call to PK with the first event record of an individual record (if the data are population data), with the first event record of the data set (if the data are single-subject data), and with a reset record. The flag A_0FLAG may be found in NONMEM- PREDPP common PROCMC. 1) Values may be assigned to reserved variables A_0(n), but only in a compartment initialization block. The value of the amount in the nth compartment (the nth element of the state vector) is set to the value assigned to A_0(n). If PK is called with a dose record or a dose-reset record where the dose is input into the nth compartment, this amount is then increased by the amount of the (bioavailable) dose. If a value is assigned to A_0(n), then it is not necessary that values be assigned to any of the remain- ing variables A_0(m). A value to the output compartment cannot be assigned. A_INITIAL(n) is a synonym for A_0(n). Perez Ruixo, Juan Jose wrote: > Dear Istvan, > > If you assume the production of the endogenous compound is zero-order process and, at baseline, your system is at steady-state, then you may want to try a code like what I paste below for one comp IV model. > > $PK > > BSL = THETA(1) * ETA(1) ;C0 in conc units > > CL = THETA(2) * ETA(2) > > KEND = BSL*CL > > V = THETA(3) * ETA(3) > > KEL = CL/V > > $DES > > DADT(1) = KEND - KEL*A(1) > > As far as the assumptions hold, the approach that “is not so good for you” should provide very similar results than the one just mentioned above for linear models, such one comp model. For non-linear models, such target mediated disposition model, the approach suggested above should work better. > > Hope it helps, > > Juanjo. > > *From:* [email protected] [ mailto: [email protected] ] *On Behalf Of *Németh István (FGYFK) > > *Sent:* lunes, 02 de mayo de 2011 7:39 > *To:* '[email protected]' > *Subject:* [NMusers] Endogenous material - C0 is not eq zero > > Dear Users! > > I tried to describe the PK of an endogenous material. I started from the example in UG VIII but after I realize that this method is not so good for me, because the amount measured in the central compartment is not the object of the DADTs. Instead of, the dadt describes a system that adjust the amount in the compartment against the so called base line level, therefore A(1) can be negative!!! Is there any method that treats situation when the C0 is not zero (I also interested to estimate C0 somehow). > > Thanks, > > István > > István Németh PhD > > Biostatistician > > Developmental Drug Metabolism & Pharmacokinetics > > Pharmacological and Drug Safety Research > > Gedeon Richter Plc > > Tel: 00 36 1 505 7082 > > Fax: 00 36 1 889 8526